Exploratory analysis of immunochemotherapy compared to chemotherapy after EGFR-TKI in non-small cell lung cancer patients with EGFR mutation: A multicenter retrospective study.

BACKGROUND: Patients with epidermal growth factor receptor (EGFR)-mutated, advanced non-small cell lung cancer have received immunochemotherapy as one of the treatment options after tyrosine kinase inhibitor (TKI) failure. METHODS: We retrospectively examined EGFR-mutant patients treated with atezolizumab-bevacizumab-carboplatin-paclitaxel (ABCP) therapy or platinum-based chemotherapy (Chemo) after EGFR-TKI therapy at five institutions in Japan. RESULTS: A total of 57 patients with EGFR mutation were analyzed. The median progression-free survival (PFS) and overall survival (OS) in the ABCP (n = 20) and Chemo (n = 37) were 5.6 and 20.9 months, 5.4 and 22.1 months, respectively (PFS, p = 0.39; OS, p = 0.61). In programmed death-ligand 1 (PD-L1)-positive patients, median PFS in the ABCP group was longer than in the Chemo group (6.9 vs. 4.7 months, p = 0.89). In PD-L1-negative patients, median PFS in the ABCP group was significantly shorter than in the Chemo group (4.6 vs. 8.7 months, p = 0.04). There was no difference in median PFS between the ABCP and Chemo groups in the subgroups of brain metastases, EGFR mutation status, or chemotherapy regimens, respectively. CONCLUSION: The effect of ABCP therapy and chemotherapy was comparable in EGFR-mutant patients in a real-world setting. The indication for immunochemotherapy should be carefully considered, especially in PD-L1-negative patients.

Efficacy and safety of immuno-chemotherapy in patients with advanced non-small-cell lung cancer harboring oncogenic mutations: a multicenter retrospective study.

PURPOSE: The effect of immuno-chemotherapy on patients with advanced non-small-cell lung cancer (NSCLC) harboring oncogenic mutations remains poorly understood. This study aimed to characterize the efficacy of immuno-chemotherapy and determine the optimal treatment strategy for such patients. METHODS: We conducted this retrospective cohort study on patients with NSCLC harboring oncogenic driver alterations and treated with an immune checkpoint inhibitor combined with chemotherapy at five institutions. The clinical characteristics and outcomes of immuno-chemotherapy for NSCLC with oncogenic mutations in a real-world setting were analyzed. RESULTS: Among 846 patients diagnosed with advanced or recurrent NSCLC between April 2017 and April 2021, 43 patients with oncogenic mutations were treated with immuno-chemotherapy. The median age of patients was 68 (range 44-78) years; 42% of patients never smoked, and adenocarcinoma was the most common histology (95%). In patients with KRAS mutations (n = 10) or PD-L1 expression of 50% or greater (n = 10), the disease control rate was 100%. The median progression-free survival (PFS) was 5.4, 6.3, and 8.9 months in patients harboring mutations in EGFR, KRAS, and other genes, respectively (P = 0.22). Patients with PD-L1 expression of 50% or greater had significantly longer median PFS than patients with PD-L1 expression of less than 50% (16.4 vs. 5.1 months; P = 0.001). Two patients experienced grade 3 immuno-related adverse events. CONCLUSION: Immuno-chemotherapy has a clinical benefit and is safe for patients with oncogenic mutations. Notably, patients with PD-L1 expression of 50% or more experience greater benefit from immuno-chemotherapy than those with PD-L1 expression of less than 50%.

Wild-type Transthyretin Amyloidosis with Diffuse Alveolar-septal Amyloidosis Diagnosed by a Transbronchial Lung Biopsy.

A 69-year-old man visited our pulmonary medicine department for dyspnea. Chest computed tomography (CT) revealed ground-glass opacity bilaterally in the lungs. Upon performing a transbronchial lung biopsy (TBLB), organizing pneumonia was diagnosed. His electrocardiogram revealed low voltage, and the cardiac ultrasound revealed hypertrophy of the interventricular septum. The patient had bilateral carpal tunnel syndrome, and amyloidosis was suspected. Congo red stain was added to the lung biopsy specimen. Amyloid deposition of transthyretin (ATTR) was positive, mutations with amino acid changes were not observed in the TTR gene. Wild-type ATTR Amyloidosis (ATTRwt amyloidosis) was diagnosed using a TBLB. Chest CT after treatment with steroids revealed diffuse alveolar-septal amyloidosis.

Abdominal pain as an initial symptom of isolated ACTH deficiency induced by nivolumab in a patient with malignant mesothelioma.

Used for a wide range of cancers, nivolumab has been reported to cause immune-related adverse events, including isolated adrenocorticotropic hormone deficiency (IAD). We report an 81-year-old woman with malignant mesothelioma who presented with abdominal pain after eight courses of nivolumab therapy, leading to the diagnosis of nivolumab-induced IAD. We should consider adrenal insufficiency (AI) when a patient on nivolumab complains of abdominal pain and has no other explanatory findings. Infusion-resistant hypotension and hyponatraemia can further suggest AI.

Lung Sound Analysis Provides A Useful Index For Both Airway Narrowing And Airway Inflammation In Patients With Bronchial Asthma.

BACKGROUND: The expiration-to-inspiration sound power ratio in a midfrequency range (E/I MF), a parameter of lung sound analysis (LSA), has been reported to be useful as an index of airway inflammation in patients with bronchial asthma. However, the E/I MF reflects airway narrowing caused by airway inflammation, and there is thus concern that it may not be an index of airway eosinophilic inflammation itself. METHODS: A total of 131 patients with bronchial asthma were classified into four groups according to the presence or absence of airway narrowing and airway inflammation to examine whether the E/I MF could serve as an index of airway inflammation. RESULTS: The E/I MF was significantly higher in patients with a normal forced expiratory volume in one second (FEV1) and high fractional exhaled nitric oxide (FeNO), those with a low FEV1 and normal FeNO, and those with a low FEV1 and high FeNO than in those with a normal FEV1 and normal FeNO (p < 0.05-0.01). In particular, the E/I MF was high even in the patients who had no airway narrowing but had airway inflammation (p < 0.01). The results of multivariate analysis of factors involved in FeNO in patients with a normal FEV1 revealed that the E/I MF was an independent factor (p = 0.0281). CONCLUSION: The E/I MF is a useful index of airway inflammation in the treatment of asthma, regardless of the presence or absence of airway narrowing.

Lung Sound Analysis and the Respiratory Cycle Dependence of Impulse Oscillometry in Asthma Patients.

Objective A lung sound analysis (LSA) is useful for detecting airway inflammation and obstruction in patients with asthma. To elucidate the mechanism of LSA, we investigated the relationship between the exhalation-to-inhalation sound pressure ratio in the low frequency range between 100 and 195 Hz (E/I LF) and the respiratory cycle dependence of impulse oscillometry (IOS) parameters. Methods Asthma patients underwent IOS [resistance of the respiratory system at 5 Hz (R5) and 20 Hz (R20), the reactance area (AX), resonant frequency of reactance (Fres), and reactance of the respiratory system at 5 Hz (X5) ], spirography, and an LSA. The correlation between the LSA-derived E/I LF values and the respiratory cycle dependence of the IOS parameters was analyzed. Patients Thirty-four patients with mild to moderate bronchial asthma, who had not received oral or inhaled corticosteroids and who had no episodes of rumbling or wheezing were examined. Results The E/I LF value was significantly correlated with the differences of the R5 and R5-R20 values between exhalation and inhalation (p=0.035 and p=0.050) in a multivariate analysis. Conclusion E/I LF appears to be an index that expresses the respiratory cycle dependence of asthma as well as IOS.

Association of airborne particles, protein, and endotoxin with emergency department visits for asthma in Kyoto, Japan.

BACKGROUND: The health effects of biological aerosols on the respiratory system are unclear. The purpose of this study was to clarify the association of airborne particle, protein, and endotoxin with emergency department visits for asthma in Kyoto City, Japan. METHODS: We collected data on emergency department visits at a hospital in Kyoto from September 2014 to May 2016. Fine (aerodynamic diameter ≤ 2.5 µm) and coarse (≥ 2.5 µm) particles were collected in Kyoto, and protein and endotoxin levels were analyzed. The association of the levels of particles, protein, endotoxin, and meteorological factors (temperature, relative humidity, wind speed, and air pressure) with emergency department visits for asthma was estimated. RESULTS: There were 1 to 15 emergency department visits for asthma per week, and the numbers of visits increased in the autumn and spring, namely many weeks in September, October, and April. Weekly concentration of protein in fine particles was markedly higher than that in coarse particles, and protein concentration in fine particles was high in spring months. Weekly endotoxin concentrations in fine and coarse particles were high in autumn months, including September 2014 and 2015. Even after adjusting for meteorological factors, the concentrations of coarse particles and endotoxin in both particles were significant factors on emergency department visits for asthma. CONCLUSIONS: Our results suggest that atmospheric coarse particles and endotoxin are significantly associated with an increased risk of asthma exacerbation.

Phenotype classification using the combination of lung sound analysis and fractional exhaled nitric oxide for evaluating asthma treatment.

BACKGROUND: We report the utility of combining lung sound analysis and fractional exhaled nitric oxide (FeNO) for phenotype classification of airway inflammation in patients with bronchial asthma. We investigated the usefulness of the combination of the expiration-to-inspiration sound power ratio in the mid-frequency range (E/I MF) of 200-400 Hz and FeNO for comprehensively classifying disease type and evaluating asthma treatment. METHODS: A total of 233 patients with bronchial asthma were included. The cutoff values of FeNO and E/I MF were set to 38 ppb and 0.36, respectively, according to a previous study. The patients were divided into 4 subgroups based on the FeNO and E/I MF cutoff values. Respiratory function, the percentages of sputum eosinophils and neutrophils, and patient background characteristics were compared among groups. RESULTS: Respiratory function was well controlled in the FeNO low/E/I MF low group (good control). Sputum neutrophil was higher and FEV1,%pred was lower in the FeNO low/E/I MF high group (poor control). History of childhood asthma and atopic asthma were associated with the FeNO high/E/I MF low group (insufficient control). The FeNO high/E/I MF high group corresponded to a longer disease duration, increased blood or sputum eosinophils, and lower FEV1/FVC (poor control). CONCLUSIONS: The combination of FeNO and E/I MF assessed by lung sound analysis allows the condition of airway narrowing and the degree of airway inflammation to be assessed in patients with asthma and is useful for evaluating bronchial asthma treatments.

Treatment evaluation using lung sound analysis in asthmatic children.

BACKGROUND AND OBJECTIVE: Non-invasive assessment of treatment and prediction of attacks in asthmatic children do not yet exist. Lung sound analysis can non-invasively evaluate airway obstruction. We used a recently developed technology for analysing lung sounds using ic700 (index of the chest wall at 700 Hz, sound intensity at 700 Hz) to evaluate response to inhaled corticosteroid (ICS) in asthmatic children. METHOD: Seventy asthmatic children, including infants, underwent lung sound recording in the asymptomatic state prior to and 1, 2, 4, 6 and 8 weeks after ICS treatment, and asthma control was assessed at 10 weeks. The ic700 scores at 4, 6 and 8 weeks were compared with the presence of attack during the following 2 weeks. Subjects were divided into uncontrolled and well-controlled groups. RESULTS: The mean ic700 scores of all subjects significantly reduced after 8 weeks of treatment. The mean scores of the uncontrolled group were significantly higher than those of the well-controlled group at 4, 6 and 8 weeks after starting treatment. The ic700 cut-off value for predicting asthma attacks within 2 weeks following the evaluation was set at 0.0. After 6 weeks of treatment, the area under the curve was 0.92 ± 0.04; the sensitivity, specificity and positive and negative predictive values were 83%, 88% and 88% and 84%, respectively. Similar results were observed at 4 and 8 weeks. CONCLUSION: The ic700 score is useful in assessing the effects of ICS treatment, predicting attack symptoms and identifying asymptomatic asthmatic children at a high risk for asthma attack.

Lung sound analysis helps localize airway inflammation in patients with bronchial asthma.

PURPOSE: Airway inflammation can be detected by lung sound analysis (LSA) at a single point in the posterior lower lung field. We performed LSA at 7 points to examine whether the technique could identify the location of airway inflammation in patients with asthma. PATIENTS AND METHODS: Breath sounds were recorded at 7 points on the body surface of 22 asthmatic subjects. Inspiration sound pressure level (ISPL), expiration sound pressure level (ESPL), and the expiration-to-inspiration sound pressure ratio (E/I) were calculated in 6 frequency bands. The data were analyzed for potential correlation with spirometry, airway hyperresponsiveness (PC20), and fractional exhaled nitric oxide (FeNO). RESULTS: The E/I data in the frequency range of 100-400 Hz (E/I low frequency [LF], E/I mid frequency [MF]) were better correlated with the spirometry, PC20, and FeNO values than were the ISPL or ESPL data. The left anterior chest and left posterior lower recording positions were associated with the best correlations (forced expiratory volume in 1 second/forced vital capacity: r=-0.55 and r=-0.58; logPC20: r=-0.46 and r=-0.45; and FeNO: r=0.42 and r=0.46, respectively). The majority of asthmatic subjects with FeNO ≥70 ppb exhibited high E/I MF levels in all lung fields (excluding the trachea) and V50%pred <80%, suggesting inflammation throughout the airway. Asthmatic subjects with FeNO <70 ppb showed high or low E/I MF levels depending on the recording position, indicating uneven airway inflammation. CONCLUSION: E/I LF and E/I MF are more useful LSA parameters for evaluating airway inflammation in bronchial asthma; 7-point lung sound recordings could be used to identify sites of local airway inflammation.

Airway inflammation phenotype prediction in asthma patients using lung sound analysis with fractional exhaled nitric oxide.

BACKGROUND: We previously reported the results of lung sound analysis in patients with bronchial asthma and demonstrated that the exhalation-to-inhalation sound pressure ratio in the low frequency range between 100 and 200 Hz (E/I LF) was correlated with the presence of airway inflammation and airway obstruction. We classified asthma patients by airway inflammation phenotype using the induced sputum eosinophil and neutrophil ratio and determined whether this phenotype could be predicted using E/I LF and fractional exhaled nitric oxide values. METHODS: Steroid-naive bronchial asthma patients were classified into four phenotypes, including "Low inflammation" (35 patients), "Eosinophilic type" (58 patients), "Neutrophilic type" (15 patients), and "Mixed type" (15 patients) based on the results of induced sputum examinations. The E/I LF data and FeNO levels were then evaluated for the four phenotype groups; the prediction powers of these two indices were then analyzed for each phenotype. RESULTS: The median E/I LF value was highest in the "Mixed type" and lowest in the "Low inflammation" group. FeNO differentiated between the "Low inflammation" and "Eosinophilic type" groups, "Low inflammation" and "Neutrophilic type" groups, and "Neutrophilic type" and "Mixed type" (p < 0.0001, p = 0.007, and p = 0.04, respectively). E/I LF differentiated between the "Low inflammation" and "Eosinophilic type" groups (p = 0.006). E/I LF could distinguish the "Mixed type" group from the "Low inflammation" and "Eosinophilic type" groups (p = 0.002). CONCLUSIONS: A combination of the E/I LF value and FeNO may be useful for the classification of the airway inflammation phenotype in patients with bronchial asthma.

Efficacy and safety of super selective bronchial artery coil embolisation for haemoptysis: a single-centre retrospective observational study.

OBJECTIVES: Evidence on the safety and long-term efficacy of super selective bronchial artery embolisation (ssBAE) using platinum coils in patients with haemoptysis is insufficient. The objective of the present study was to evaluate the safety and the 3-year postprocedure haemoptysis-free survival rate of de novo elective ssBAE using platinum coils rather than particles for the treatment of haemoptysis. DESIGN: A single-centre retrospective observational study. SETTING: Hemoptysis and Pulmonary Circulation Center in Japan. PARTICIPANTS: A total of 489 consecutive patients with massive and non-massive haemoptysis who underwent de novo elective ssBAE without malignancy or haemodialysis. INTERVENTIONS: ssBAE using platinum coils. All patients underwent CT angiography before the procedure for identifying haemoptysis-related arteries (HRAs) and for procedural planning. PRIMARY AND SECONDARY OUTCOME MEASURES: The composite of the 3-year recurrence of haemoptysis and mortality from the day of the last ssBAE session. Each component of the primary end point and procedural success defined as successful embolisation of all target HRAs were also evaluated. RESULTS: The median patient age was 69 years, and 46.4% were men. The total number of target vessels was 4 (quartile 2-7), and the procedural success rate was 93.4%. There were 8 (1.6%) major complications: 1 aortic dissection, 2 symptomatic cerebellar infarctions and 5 mediastinal haematoma cases. The haemoptysis-free survival rates were estimated by the Kaplan-Meier analysis at 86.9% (95% CI 83.7% to 90.2%) at 1 year, 79.4% (74.8% to 84.3%) at 2 years and 57.6% (45.1% to 73.4%) at 3 years. Although not statistically significant by the adjusted analysis of variance with multiple imputation of missing variables, cryptogenic haemoptysis tended to show the most favourable outcome and non-tuberculous mycobacterium showed the worst outcome (adjusted p=0.250). CONCLUSIONS: We demonstrated the safety and long-term efficacy of elective ssBAE using platinum coils and established that it can be a valuable therapeutic option for treating patients with haemoptysis.

Pulmonary Tumor Thrombotic Microangiopathy Caused by a Parotid Tumor: Early Antemortem Diagnosis and Long-term Survival.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a high-mortality disease that is difficult to diagnose clinically. Our patient was an 80-year-old woman who came to us due to symptoms of increasing dyspnea. A clinical evaluation showed that she had hypoxemia and pulmonary arterial hypertension without any abnormalities in the major pulmonary arteries, bronchi, or alveoli. A lung perfusion scan showed multiple wedge-shaped perfusion defects. Further examination revealed adenocarcinoma in her right parotid gland with metastasis to the submandibular lymph nodes. We diagnosed her to have PTTM caused by a parotid tumor. The patient survived for 11 months with chemotherapy. An early antemortem diagnosis by minimally invasive examinations will help PTTM patients to survive longer.

Peripheral bronchial obstruction evaluation in patients with asthma by lung sound analysis and impulse oscillometry.

BACKGROUND: Computer-aided lung sound analysis (LSA) has been reported to be useful for evaluating airway inflammation and obstruction in asthma patients. We investigated the relation between LSA and impulse oscillometry with the evaluation of peripheral airway obstruction. METHODS: A total of 49 inhaled corticosteroid-naive bronchial asthma patients underwent LSA, spirometry, impulse oscillometry, and airway hyperresponsiveness testing. The data were analyzed to assess correlations between the expiration: inspiration lung sound power ratio (dB) at low frequencies between 100 and 195 Hz (E/I LF) and various parameters. RESULTS: E/I LF and X5 were identified as independent factors that affect V˙50,%predicted. E/I LF showed a positive correlation with R5 (r = 0.34, p = 0.017), R20 (r = 0.34, p = 0.018), reactance area (AX, r = 0.40, p = 0.005), and resonant frequency of reactance (Fres, r = 0.32, p = 0.024). A negative correlation was found between E/I LF and X5 (r = -0.47, p = 0.0006). E/I LF showed a negative correlation with FEV1/FVC(%), FEV1,%predicted, V˙50,%predicted, and V˙25,%predicted (r = -0.41, p = 0.003; r = -0.44, p = 0.002; r = -0.49, p = 0.0004; and r = -0.30, p = 0.024, respectively). E/I LF was negatively correlated with log PC20 (r = -0.30, p = 0.024). Log PC20, X5, and past smoking were identified as independent factors that affected E/I LF level. CONCLUSIONS: E/I LF as with X5 can be an indicator of central and peripheral airway obstruction in bronchial asthma patients.

Lung sound analysis can be an index of the control of bronchial asthma.

BACKGROUND: We assessed whether lung sound analysis (LSA) is a valid measure of airway obstruction and inflammation in patients with bronchial asthma during treatment with inhaled corticosteroids (ICSs). METHODS: 63 good adherence patients with bronchial asthma and 18 poor adherence patients were examined by LSA, spirometry, fractional exhaled nitric oxide (FeNO), and induced sputum. The expiration-to-inspiration lung sound power ratio at low frequencies between 100 and 200 Hz (E/I LF) obtained by LSA was compared between healthy volunteers and bronchial asthma patients. Next, post-ICS treatment changes were compared in bronchial asthma patients between the good adherence patients and the poor adherence patients. RESULTS: E/I LF was significantly higher in bronchial asthma patients (0.62 ± 0.21) than in healthy volunteers (0.44 ± 0.12, p < 0.001). The good adherence patients demonstrated a significant reduction in E/I LF from pre-treatment to post-treatment (0.55 ± 0.21 to 0.46 ± 0.16, p = 0.002), whereas the poor adherence patients did not show a significant change. The decrease of E/I LF correlated with the improvement of FEV1/FVC ratio during the ICS treatment (r = -0.26, p = 0.04). The subjects with higher pre-treatment E/I LF values had significantly lower FEV1/FVC and V50,%pred (p < 0.001), and significantly higher FeNO and sputum eosinophil percentages (p = 0.008 and p < 0.001, respectively). CONCLUSIONS: The E/I LF measurement obtained by LSA is useful as an indicator of changes in airway obstruction and inflammation and can be used for monitoring the therapeutic course of bronchial asthma patients.

Changes in lung sounds during asthma progression in a guinea pig model.

BACKGROUND: Lung sound analysis is useful for objectively evaluating airways even in children with asymptomatic asthma. However, the relationship between lung sounds and morphological changes in the airways has not been elucidated. We examined the relationship between lung sounds and chronic morphological changes in the airways during the progression of asthma from onset in guinea pigs. METHODS: Eleven male guinea pigs were examined; of these, seven were used as asthma models and four as controls. The asthma models were sensitized and repeatedly challenged by inhaling albumin chicken egg. We measured lung sounds and lung function twice a week for 21 weeks. After the final antigen challenge, the lungs were excised for histological examination. We measured the ratio of airway wall thickness to the total airway area and the ratio of the internal area to the total airway area in the trachea, third bronchi, and terminal bronchioles. RESULTS: Among the lungs sounds, the difference between the two groups was greatest with respect to inspiratory sound intensity. The ratio of airway wall thickness to the total airway area of the terminal bronchioles was greater in the asthma models than in the controls, and it correlated best with the changes in inspiratory sound intensity in the 501-1000-Hz range (r = 0.76, p < 0.003). CONCLUSIONS: Lung sound intensity in the middle frequency range from 501 to 1000 Hz correlated with peripheral airway wall thickness. Inspiratory sound intensity appeared to be an indicator of morphological changes in small airways in asthma.

Lung Sound Analysis and Airway Inflammation in Bronchial Asthma.

BACKGROUND: Our previous study on lung sound analysis (LSA) revealed that the expiration-to-inspiration sound power ratio in a low-frequency range (E/I LF) was increased in patients with bronchial asthma, even when they have no wheezes. OBJECTIVE: We also monitored the expiration-to-inspiration sound power ratio in a mid-frequency range (E/I MF) and the mid- to low-frequency sound power ratio for inspiration and expiration (ie, I MF/LF and E MF/LF, respectively) using a new software program to examine which parameter is most suitable as an index of airway inflammation in patients with asthma. METHODS: A study was conducted in 31 patients with mild-to-moderate bronchial asthma to examine potential correlations of LSA parameters (E/I LF, E/I MF, I MF/LF, and E MF/LF) with spirogram parameters, airway hyperresponsiveness (PC20), fractional exhaled nitric oxide (NO), and sputum eosinophils. RESULTS: E/I LF was significantly correlated with airway narrowing (forced expiratory volume in 1 second [FEV1.0]/forced vital capacity [FVC]%: r = -0.50, maximal expiratory flow at 50% [V50],%pred: r = -0.50) and peripheral airway inflammation (alveolar NO: r = 0.36, eosinophils in peripheral sputum: r = 0.41). E/I MF was significantly correlated with airway narrowing (FEV1.0/FVC%: r = -0.46, V50,%pred: r = -0.49), airway inflammation (bronchial NO: r = 0.43, alveolar NO: r = 0.47, eosinophils in peripheral sputum: r = 0.50), and airway hyperresponsiveness (logPC20: r = -0.49). E MF/LF was significantly correlated with airway inflammation (NO: r = 0.36, eosinophils in sputum: r = 0.40) and airway hyperresponsiveness (logPC20: r = -0.40). I MF/LF was not significantly correlated with any parameters. CONCLUSIONS: Among the 4 LSA parameters investigated, E/I MF demonstrated the highest correlation with airway inflammation, and also with bronchial hyperresponsiveness.

Evaluation of airflow limitation using a new modality of lung sound analysis in asthmatic children.

BACKGROUND: Reliable assessment of not only symptoms but also lung function is essential in asthma management. We developed a new technology for analyzing lung sounds and assessed its clinical usefulness in asthmatic children. METHODS: Forty-four children underwent lung sound recording with simultaneous airflow measurement using a sensor on the upper right anterior chest. We calculated a sound parameter index from the amplitude of inspiratory lung sounds at 700 Hz (ic700). ic700 were compared depending on flow and body size. In addition, 184 asthmatic children and 16 non-asthmatic children underwent lung sound analysis and lung function test in an asymptomatic state. In the asthma group, 135 children received treatment continually. The untreated asthma group included 28 children who had never received treatment continually and 21 children who had not been treated for at least 1 year. The asthmatic children were divided into four classes according to asthma severity. ic700 were compared depending on spirometric parameters and asthma severity classification. RESULTS: The influences of flow and body size were negligible for ic700. ic700 correlated with FEV1%, MMF and FEF50 (r = -0.436, -0.339 and -0.302, respectively). There was a significant difference of ic700 between asthmatic and non-asthmatic children (p < 0.001), and ic700 correlated with the classification of asthma severity (p < 0.001). The ic700 scores of the severe group were higher than those of the intermittent group and non-asthmatic children. CONCLUSIONS: It was possible to evaluate airway dysfunction of asthma using ic700, which was calculated non-invasively by analyzing lung sounds alone, without measuring body size and airflow.

Prediction of airway inflammation in patients with asymptomatic asthma by using lung sound analysis.

BACKGROUND: The intensity and frequency of sounds in a lung sound analysis (LSA) may be related to airway constriction; however, whether any factors of an LSA can predict airway eosinophilic inflammation in patients with asthma is unknown. OBJECTIVE: To determine whether an LSA can predict airway eosinophilic inflammation in patients with asymptomatic asthma. METHODS: The expiratory-inspiratory ratios of sound power in the low-frequency range (E-I LF) from 36 patients with asymptomatic asthma were compared with those of 14 healthy controls. The relations of E-I LF with airway eosinophilic inflammation were analyzed. The E-I LF cutoff value for predicting airway eosinophilic inflammation also was analyzed. RESULTS: The mean ± SD E-I LF was higher in the patients with asthma and with increased sputum eosinophils than in those patients without increased sputum eosinophils (0.45 ± 0.24 vs 0.20 ± 0.12; P < .001) or in the healthy controls (0.25 ± 0.10; P = .003). A multiple regression analysis showed that the sputum eosinophil ratio and exhaled nitric oxide were independently correlated with E-I LF, P = .0003 and P = .032, respectively. For the prediction of increased sputum eosinophils and increased fractional exhaled nitric oxide levels, the E-I LF thresholds of 0.29 and 0.30 showed sensitivities of 0.80 and 0.74 and specificities of 0.83 and 0.77, respectively. CONCLUSIONS: We showed that LSAs can safely predict airway inflammation of patients with asymptomatic asthma.

A New Modality Using Breath Sound Analysis to Evaluate the Control Level of Asthma.

BACKGROUND: Reliable symptom assessment is essential in asthma management. We developed new technology for analyzing breath sounds and assessed its clinical usefulness for monitoring asthmatic children. METHODS: Eighty asthmatic children and 59 non-asthmatic children underwent breath sound analysis in an asymptomatic state. Their asthma control was assessed by the Asthma Control TestTM or Childhood ACTTM scores and divided into two groups, namely, well-controlled (perfect) (n = 19) and not well-controlled (not perfect) (n = 61). Breath sounds were recorded using two sensors, located on the right anterior chest and trachea. We calculated the acoustic transfer characteristics between the two points, which indicated the relationship between frequencies and attenuation during breath sound propagation. Two indices of sound parameters, the chest wall sound index (CWI) and the tracheal sound index (TRI), were calculated from the transfer characteristics and tracheal sounds. We also developed a new parameter, the breath sound index (BSI), on a 2-dimensional diagram of CWI and TRI and tried to determine whether BSI may clarify asthma control better than CWI or TRI alone. RESULTS: There was a significant difference in TRI and BSI between asthmatic and non-asthmatic children (p = 0.007, p < 0.001). There was a significant difference in CWI and TRI between the well-controlled and not-wellcontrolled groups (p < 0.001). BSI discriminated between the two groups accurately (p < 0.001). The sensitivity and specificity of BSI for asthma control were 83.6% and 84.2%, respectively. CONCLUSIONS: Asthma control could be evaluated using a new index calculated from breath sound analysis.